Effect of pH on potassium and proton conductance in renal proximal tubule.

The effect of intracellular and extracellular pH on potassium conductance (GK) was examined in isolated amphibian (Rana pipiens) proximal tubule cells under whole cell voltage clamp conditions. Internal perfusion of the patch pipette was used to precisely control intracellular pH. In the region of normal resting potential (-51 +/- 3 mV), raising cell pH from 6.5 to 8.0 did not significantly increase GK (1.1 +/- 0.3 vs. 1.3 +/- 0.3 nS; P > 0.08, n = 8). Similar elevations in external (bath) pH had even less of an effect on GK. In contrast, when cells were voltage clamped to 30 mV more negative than the resting potential, raising internal pH from 6.5 to 8.0 did increase GK from 1.05 +/- 0.3 to 1.8 +/- 0.5 nS (P < 0.04; n = 8). These results suggest that modest changes in pH have little effect on GK, except at large negative potentials. In the process of examining the pH dependence of GK, a slowly activating, voltage-dependent conductance of 7.5 +/- 1 nS (n = 20; for 20 microns cells) was observed during cell depolarization. Although the instantaneous current-voltage relation of this conductance was linear, its marked voltage dependence produced an apparent steady-state rectification, with Gm = 0.5 +/- 0.2 nS and Gout = 9.0 +/- 1 nS (n = 11). Outward current was reversibly blocked by 3 mM Cu, Cd, or Co. In the absence of Na, K, and Ca (and only trace amounts of Cl), rapid changes in bath pH from 6.5 to 8.0 shifted the steady-state reversal potential (Erev) by -37 +/- 4 mV (n = 9) and the instantaneous Erev by -56 +/- 4 mV (n = 9). These shifts in Erev were consistent with a hydrogen ion conductance (GH), similar to what has been reported for snail neuron, neutrophils, alveolar epithelial cells, and phagocytes. Since the magnitude of this GH would be insignificant at resting cell pH and membrane potential, its role in renal proximal tubule under normal conditions is somewhat obscure. Nonetheless, in pathological situations, GH could function to prevent acid overload during any process that depolarizes the cell, such as low temperature or metabolic inhibition.